Details

Autor(en) / Beteiligte

• Blank, Thomas
• Detje, Claudia N.
• Spieß, Alena
• Hagemeyer, Nora
• Brendecke, Stefanie M.
• Wolfart, Jakob
• Staszewski, Ori
• Zöller, Tanja
• Papageorgiou, Ismini
• Schneider, Justus
• Paricio-Montesinos, Ricardo
• Eisel, Ulrich L.M.
• Manahan-Vaughan, Denise
• Jansen, Stephan
• Lienenklaus, Stefan
• Lu, Bao
• Imai, Yumiko
• Müller, Marcus
• Goelz, Susan E.
• Baker, Darren P.
• Schwaninger, Markus
• Kann, Oliver
• Heikenwalder, Mathias
• Kalinke, Ulrich
• Prinz, Marco

Titel

Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment

Ist Teil von

• Immunity (Cambridge, Mass.), 2016-04, Vol.44 (4), p.901-912

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded RNA ligands, and IFNs shared pathways involving engagement of melanoma differentiation-associated protein 5 (MDA5), retinoic acid-inducible gene 1 (RIG-I), and mitochondrial antiviral signaling protein (MAVS), and subsequently induced IFN responses specifically in brain endothelia and epithelia of mice. Behavioral alterations were specifically dependent on brain endothelial and epithelial IFN receptor chain 1 (IFNAR). Using gene profiling, we identified that the endothelia-derived chemokine ligand CXCL10 mediated behavioral changes through impairment of synaptic plasticity. These results identified brain endothelial and epithelial cells as natural gatekeepers for virus-induced sickness behavior, demonstrated tissue specific IFNAR engagement, and established the CXCL10-CXCR3 axis as target for the treatment of behavioral changes during virus infection and type I IFN therapy. [Display omitted] •Viruses induce depressive behavior and ISG15 expression at the blood-brain barrier•IFNAR1 expression on neural cells is not involved in IFN-β-induced sickness behavior•IFNAR1 expression on brain endothelial and epithelial cells drives behavioral changes•Brain endothelia- and epithelia-derived CXCL10 inhibits hippocampal synaptic plasticity Sickness behavior and cognitive dysfunction occur frequently during RNA virus infection by unknown mechanisms. Prinz and colleagues show that virus-induced sickness behavior is induced by interferon receptor chain 1 (IFNAR1) engagement on brain endothelial and epithelial cells that in turn influence neuronal signaling to drive cognitive impairment and depression-like behavior.